Development of Novel Therapeutics for Asthma

Development of Novel Therapeutics for Asthma BioTherapeutics Inc (BTI) is an emerging biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel precision medicine therapeutics for asthma, allergy and autoimmune diseases. An unmet clinical need for safer, more effective drugs for asthma remains as current therapies have limited efficacy and adverse side effects. Asthma is a chronic, widespread allergic disease with total expenses exceeding $80 billion annually in the U.S. Current therapies for asthma are modestly effective with significant side effects. Specifically, type 2 asthma patients can develop steroid dependency in neutrophilic asthma, while non-type 2 asthma has a lower responsiveness to current treatments. Recent attempts to target this population have been unsuccessful, with anti-TNF, anti-IL-17 receptor and chemokine inhibitors failing in clinical trials, while macrolides and methotrexate have shown mild improvement but at high side effect risk. Thus, there is an unmet medical need for safer and more efficacious asthma therapeutics. In the last years, regulatory T (Treg) cells have gained increased recognition in the treatment of inflammatory and allergic diseases. Furthermore, metabolic dysregulation has also been associated with the pathogenesis of this complex disorder. Immunometabolic manipulation of Treg cells to restore their suppressive capacity has been postulated as a promising novel therapeutic approach for asthma. Indeed, in asthma patients, Treg cells present deficient suppressive ability. Administration of Tregs in animal models of allergic asthma can resolve the established chronic inflammation. Moreover, targeting of glucose and oxidative metabolism have also resulted in decreased inflammation and airway hyperresponsiveness. This SBIR Phase I application will develop a novel immunoregulatory and immunometabolic therapeutic for the treatment of asthma. The Specific Aims are to: Aim 1. Determine the safety profile and pharmacokinetics (PK) of the new immunoregulatory therapeutic by evaluating oral bioavailability and distribution and conducting general toxicity studies in rats. Aim 2. Characterize the therapeutic efficacy and route of administration of the new immunoregulatory therapeutic using ovalbumin and house dust mite induced models of neutrophilic asthma. Efficacy studies will be determined by airway resistance, lung histopathology, flow cytometry and cytokine expression. Expected successful outcomes are: i) ≥ 50 % decrease in lung histological lesions and ≥40% decreased infiltration of eosinophils and neutrophils in the lungs; ii) ≥ 50% suppression of airway resistance; iii) ≥ 50% decreased infiltration of neutrophils in the lungs of treated mice; and iv) lung concentrations ≥ 25 ng/g and NOAEL ≥ 1,000 mg/kg in rats. Commercial Application: The impact of this new, oral, immunoregulatory asthma drug has the potential to address the unmet needs of 27 million U.S. patients and disrupt an global market of $20 billion/yr by 2026.